RESUMO
BACKGROUND: More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing. METHODS: Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group. RESULTS: Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia. CONCLUSIONS: In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.
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COVID-19 , Pessoal de Saúde , Transtornos do Olfato , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Feminino , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/virologia , Adulto , Prevalência , Estudos de Casos e Controles , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Olfato/fisiologiaRESUMO
Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity, the olfactory epithelium (OE) is particularly sensitive to infections which may lead to olfactory dysfunction. In patients suffering from coronavirus disease 2019, deficits in olfaction have been characterized as a distinctive symptom. Here, we used the K18hACE2 mice to study the spread of SARS-CoV-2 infection and inflammation in the olfactory system (OS) after 7â d of infection. In the OE, we found that SARS-CoV-2 selectively targeted the supporting/sustentacular cells (SCs) and macrophages from the lamina propria. In the brain, SARS-CoV-2 infected some microglial cells in the olfactory bulb (OB), and there was a widespread infection of projection neurons in the OB, piriform cortex (PC), and tubular striatum (TuS). Inflammation, indicated by both elevated numbers and morphologically activated IBA1+ cells (monocyte/macrophage lineages), was preferentially increased in the OE septum, while it was homogeneously distributed throughout the layers of the OB, PC, and TuS. Myelinated OS axonal tracts, the lateral olfactory tract, and the anterior commissure, exhibited decreased levels of 2',3'-cyclic-nucleotide 3'-phosphodiesterase, indicative of myelin defects. Collectively, our work supports the hypothesis that SARS-CoV-2 infected SC and macrophages in the OE and, centrally, microglia and subpopulations of OS neurons. The observed inflammation throughout the OS areas and central myelin defects may account for the long-lasting olfactory deficit.
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COVID-19 , Bainha de Mielina , Bulbo Olfatório , Mucosa Olfatória , SARS-CoV-2 , Animais , COVID-19/patologia , COVID-19/complicações , Camundongos , Mucosa Olfatória/patologia , Mucosa Olfatória/virologia , Bulbo Olfatório/patologia , Bulbo Olfatório/virologia , Bainha de Mielina/patologia , Bainha de Mielina/metabolismo , Microglia/patologia , Microglia/metabolismo , Microglia/virologia , Camundongos Transgênicos , Enzima de Conversão de Angiotensina 2/metabolismo , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Modelos Animais de Doenças , Masculino , Inflamação/patologia , Inflamação/virologia , Macrófagos/patologia , FemininoRESUMO
After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.
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COVID-19 , Disfunção Cognitiva , Fadiga , Imageamento por Ressonância Magnética , Transtornos do Olfato , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , COVID-19/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/virologia , Masculino , Fadiga/fisiopatologia , Feminino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico por imagem , Transtornos do Olfato/virologia , Transtornos do Olfato/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Síndrome de COVID-19 Pós-Aguda , IdosoRESUMO
Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system. OBJECTIVE: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders. MATERIAL AND METHODS: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale. RESULTS: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system. CONCLUSION: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.
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COVID-19 , Transtornos do Olfato , Nervo Trigêmeo , Humanos , COVID-19/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/virologia , Nervo Trigêmeo/fisiopatologia , SARS-CoV-2 , Idoso , Olfato/fisiologia , Olfatometria/métodos , Anosmia/etiologia , Anosmia/fisiopatologia , Federação Russa/epidemiologia , Doenças do Nervo Trigêmeo/fisiopatologia , Doenças do Nervo Trigêmeo/etiologia , Doenças do Nervo Trigêmeo/diagnósticoRESUMO
Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Idoso , Sensibilidade e Especificidade , Odorantes , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/virologia , Adulto JovemRESUMO
INTRODUCTION: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction. METHODS: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset. RESULTS: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets. CONCLUSION: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.
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COVID-19 , Transtornos do Olfato , Humanos , COVID-19/epidemiologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/virologia , Criança , Feminino , Masculino , Estudos Retrospectivos , Pré-Escolar , Adolescente , SARS-CoV-2 , Pandemias , Infecções Respiratórias/epidemiologia , LactenteRESUMO
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD.
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COVID-19 , Doenças Neuroinflamatórias , Transtornos do Olfato , Doença de Parkinson , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/fisiopatologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/fisiopatologia , Doenças Neuroinflamatórias/imunologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Transtornos do Olfato/virologia , Bulbo Olfatório/fisiopatologia , Bulbo Olfatório/virologia , Bulbo Olfatório/patologiaRESUMO
OBJECTIVE: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss. METHODS: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores. RESULTS: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function. CONCLUSION: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.
Assuntos
COVID-19 , Transtornos do Olfato , SARS-CoV-2 , Humanos , COVID-19/complicações , Transtornos do Olfato/etiologia , Transtornos do Olfato/virologia , Transtornos do Olfato/reabilitação , Transtornos do Olfato/terapia , Estudos de Casos e Controles , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Olfato/fisiologia , Anosmia/etiologia , Treinamento OlfativoRESUMO
Much - possibly even too much - has been published about chemosensory dysfunction as a consequence of COVID-19. Studies have reported prevalence of taste loss in up to 89.9%, which is in a similar range as COVID-19 related smell loss. However, most of these publications rely solely on patients' self-reports. Only few studies used validated psychophysical tests to specifically address olfaction and gustation. Especially for gustation, it is evident that subjective reporting does not correlate well with more objective psychophysical findings, often leading to an overestimation of subjectively impaired taste.
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COVID-19 , SARS-CoV-2 , Distúrbios do Paladar , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Prevalência , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/virologia , Distúrbios do Paladar/etiologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/virologia , Transtornos do Olfato/etiologiaRESUMO
BACKGROUND: Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD). METHODS: Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts. RESULTS: Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05). CONCLUSION: SGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.
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Bloqueio Nervoso Autônomo , COVID-19 , Transtornos do Olfato , Gânglio Estrelado , Humanos , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Bloqueio Nervoso Autônomo/métodos , Estudos Retrospectivos , Transtornos do Olfato/virologia , Transtornos do Olfato/terapia , Idoso , Adulto , SARS-CoV-2 , Resultado do TratamentoRESUMO
OBJECTIVE: Smell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX research network. METHODS: Two queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders. RESULTS: The overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza. CONCLUSIONS: Disorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported.
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COVID-19 , Influenza Humana , Transtornos do Olfato , Distúrbios do Paladar , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/virologia , Distúrbios do Paladar/etiologia , Incidência , Estudos Retrospectivos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Masculino , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/virologia , Transtornos do Olfato/etiologia , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos de CoortesRESUMO
OBJECTIVE: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. DATA SOURCES: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. REVIEW METHODS: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. RESULTS: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. CONCLUSION: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.
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Administração Intranasal , COVID-19 , Transtornos do Olfato , Humanos , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/etiologia , Transtornos do Olfato/virologia , COVID-19/complicações , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Resultado do Tratamento , Glucocorticoides/uso terapêutico , Glucocorticoides/administração & dosagemRESUMO
BACKGROUND: The purpose of this study was to compare the prevalence of olfactory dysfunction (OD) at different stages of the COVID-19 pandemic by evaluating subjects diagnosed with SARS-CoV-2 infection during the Omicron wave with psychophysical tests and comparing the results with those obtained from patients infected during the D614G, Alpha and Delta waves and with those of a control group. METHODOLOGY: The study included adult patients diagnosed with SARS-CoV-2 infection. Depending on the time of diagnosis, the subjects were divided into four study groups: D614G; Alpha, Delta and Omicron variant groups. A group of uninfected individuals was used as control. All subjects underwent psychophysical evaluation of the olfactory function with the Connecticut Chemosensory Clinical Research Center olfactory test (D614G and Alpha groups) or the extended version of the Sniffin'Sticks test (Delta, Omicron and control groups). RESULTS: 372 cases (134 D614G group, 118 Alpha group, 32 in Delta group and 88 Omicron group) were recruited and evaluated within 10 days of infection, alongside 80 controls. Patients self-reported olfactory loss in 72.4% of cases in the D614G group, in 75.4% of cases in the Alpha group, in 65.6% of cases in the Delta group and in 18.1% in the Omicron group. Psychophysical evaluation revealed a prevalence of OD: 80.6%, 83.0%, 65.6% and 36.3% in the D614G, Alpha, Delta and Omicron group respectively. The differences between the D614G, Alpha and Delta groups were not statistically significant. The Omicron group demonstrated a significantly lower prevalence of OD than the other variants but still significantly higher than the controls. CONCLUSIONS: During the Omicron wave OD was less prevalent than during the D614G, Alpha and Delta periods. One-third of patients have reduced olfactory function on psychophysical evaluation during the Omicron wave. Our results should be considered with caution as the VOC has not been determined with certainty.
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COVID-19 , Transtornos do Olfato , SARS-CoV-2 , Adulto , Humanos , Estudos de Casos e Controles , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/virologia , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/virologia , Pandemias , PrevalênciaRESUMO
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.
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Betacoronavirus 1 , COVID-19 , Infecções por Coronavirus/patologia , Transtornos do Olfato , Animais , Betacoronavirus 1/fisiologia , Humanos , Camundongos , Transtornos do Olfato/virologia , SARS-CoV-2 , Olfato , SuínosRESUMO
Objective: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID". Methods: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2. Results: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021. Conclusions: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.
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COVID-19 , Transtornos do Olfato , Distúrbios do Paladar , COVID-19/complicações , Transtornos da Audição/diagnóstico , Transtornos da Audição/virologia , Humanos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/virologia , SARS-CoV-2 , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/virologia , Vertigem/diagnóstico , Vertigem/virologia , Síndrome de COVID-19 Pós-AgudaRESUMO
OBJECTIVE: Alterations of the olfactory function in patients affected by COVID-19 often have an early onset and a variable duration ranging from a few weeks to months. The aim of this study was to evaluate olfactory dysfunction persistence after recovery from COVID-19, and potential related clinical-demographic conditions. PATIENTS AND METHODS: A total of 76 patients recovered from COVID-19 from at least 20 days with olfactory dysfunction during the infection were included in the study. For the subjective evaluation of olfactory function, a visual analogic scale (VAS) was used. The objective evaluation was performed with the use of the Sniffin' Sticks test. RESULTS: Objective assessment of olfactory function revealed that 48 (63.16%) patients were found to be normosmic (TDI ≥ 30.5), 26 (34.21%) were hyposmic (TDI from 30.5 to 16.5) and two (2.63%) were anosmic (TDI ≤ 16.5) at the time of the evaluation. These results did not show a significant difference between subjective and objective tests (p = 0.45). Most patients recovered their sense of smell within the first two months after recovery while a portion (22.2%) still experienced olfactory alterations 4-6 months after SARS-CoV-2 infection. Patients who had not recovered their sense of smell had a significantly longer period of SARS-CoV-2 positivity compared to patients that fully recovered (36.07 ± 7.78 days vs. 29 ± 7.89 days; p = 0.04). CONCLUSIONS: Our results suggest that the duration of the infection negatively correlates with the recovery of olfactory function.
Assuntos
COVID-19/epidemiologia , Transtornos do Olfato/epidemiologia , Adolescente , Adulto , Idoso , Anosmia/epidemiologia , Anosmia/etiologia , Anosmia/virologia , COVID-19/complicações , COVID-19/virologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Transtornos do Olfato/virologia , Estudos Prospectivos , Recuperação de Função Fisiológica , SARS-CoV-2 , Olfato , Adulto JovemRESUMO
IMPORTANCE: Current tools for diagnosis of olfactory dysfunction (OD) are costly, time-consuming, and often require clinician administration. OBJECTIVE: To develop and validate a simple screening assessment for OD using common household items. DESIGN, SETTING, AND PARTICIPANTS: This fully virtual diagnostic study included adults with self-reported OD from any cause throughout the US. Data were collected from December 2020 to April 2021 and analyzed from May 2021 to July 2021. MAIN OUTCOMES AND MEASURES: Participants with self-reported olfactory dysfunction took a survey assessing smell perception of 45 household items and completed the Clinical Global Impression-Severity (CGI-S) smell questionnaire, the University of Pennsylvania Smell Identification Test (UPSIT), and the 36-item Short Form Survey (SF-36). Psychometric and clinimetric analyses were used to consolidate 45 household items into 2 short Novel Anosmia Screening at Leisure (NASAL) assessments, NASAL-7 (range, 0-14; lower score indicating greater anosmia) and NASAL-3 (range, 0-6; lower score indicating greater anosmia). RESULTS: A total of 115 participants were included in the study, with a median (range) age of 42 (19-70) years, 92 (80%) women, and 97 (84%) White individuals. There was a moderate correlation between the UPSIT and NASAL-7 scores and NASAL-3 scores (NASAL-7: ρ = 0.484; NASAL-3: ρ = 0.404). Both NASAL-7 and NASAL-3 had moderate accuracy in identifying participants with anosmia as defined by UPSIT (NASAL-7 area under the receiver operating curve [AUC], 0.706; 95% CI, 0.551-0.862; NASAL-3 AUC, 0.658; 95% CI, 0.503-0.814). Scoring 7 or less on the NASAL-7 had 70% (95% CI, 48%-86%) sensitivity and 53% (95% CI, 43%-63%) specificity in discriminating participants with anosmia from participants without. Scoring 2 or less on the NASAL-3 had 57% (95% CI, 36%-76%) sensitivity and 78% (95% CI, 69%-85%) specificity in discriminating participants with anosmia from participants without. There was moderate agreement between UPSIT-defined OD categories and those defined by NASAL-7 (weighted κ = 0.496; 95% CI, 0.343-0.649) and those defined by NASAL-3 (weighted κ = 0.365; 95% CI, 0.187-0.543). The agreement with self-reported severity of olfactory dysfunction as measured by CGI-S and the NASAL-7 and NASAL-3 was moderate, with a weighted κ of 0.590 (95% CI, 0.474-0.707) for the NASAL-7 and 0.597 (95% CI, 0.481-0.712) for the NASAL-3. CONCLUSION AND RELEVANCE: The findings of this diagnostic study suggest that NASAL-7 and NASAL-3, inexpensive and brief patient-reported assessments, can be used to identify individuals with OD. As the burden of COVID-19-associated OD increases, these assessments may prove beneficial as screening and diagnostic tools. Future work will explore whether the NASAL assessments are sensitive to change and how much of a change is clinically important.
Assuntos
COVID-19/complicações , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/virologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Kit de Reagentes para Diagnóstico , SARS-CoV-2 , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To characterize the clinical features, risk factors, symptom time-course, and quality of life implications for parosmia among coronavirus disease (COVID)-related olfactory dysfunction patients. METHODS: Individuals with olfactory dysfunction associated with laboratory-confirmed or clinically suspected COVID-19 infection were recruited from otolaryngology and primary care practices over a period from August 2020 to March 2021. Participants completed olfactory dysfunction and quality of life surveys. RESULTS: A total of 148 (64.1%) of 231 respondents reported parosmia at some point. Parosmia developed within 1 week of any COVID-19 symptom onset in 25.4% of respondents, but more than 1 month after symptom onset in 43.4% of respondents. Parosmia was associated with significantly better quantitative olfactory scores on Brief Smell Identification Test (8.7 vs. 7.5, P = .006), but demonstrated worse quality of life scores, including modified brief Questionnaire of Olfactory Dysfunction-Negative Statements and Sino-Nasal Outcome Test-22 scores (12.1 vs. 8.5, P < .001; 26.2 vs. 23.2, P = .113). Participants who developed parosmia at any point were significantly younger and less likely to have history of chronic sinusitis than those who did not develop parosmia (40.2 vs. 44.9 years, P = .007; 7.2% vs. 0.7%, P = .006). CONCLUSION: COVID-19-associated olfactory dysfunction is frequently linked with development of parosmia, which often presents either at onset of smell loss or in a delayed fashion. Despite better quantitative olfactory scores, respondents with parosmia report decreased quality of life. A majority of respondents with persistent parosmia have sought treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:633-639, 2022.